Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice
Abstract Background Vascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the stria...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12864-025-11256-y |
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| author | Shijia Le Fengyiyang Xu Zhi Luo Weihao Shi Shuangshuang Lu Zengyu Zhang Zimin Guo Wenshi Xu Mingqi Yang Tianyi Li Xu Li Kun Liang Lei Zhu |
| author_facet | Shijia Le Fengyiyang Xu Zhi Luo Weihao Shi Shuangshuang Lu Zengyu Zhang Zimin Guo Wenshi Xu Mingqi Yang Tianyi Li Xu Li Kun Liang Lei Zhu |
| author_sort | Shijia Le |
| collection | DOAJ |
| description | Abstract Background Vascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the striatum, a brain region critical for motor function and cognition, following chronic hypoperfusion using a bilateral common carotid artery stenosis (BCAS) model in mice. Methods RNA-seq was utilized to identify differentially expressed genes (DEGs) associated with hypoperfusion. In parallel, ATAC-seq was used to assess changes in chromatin accessibility within the striatum, providing insight into the epigenome and potential regulatory mechanisms. The integration of these datasets allowed us to correlate chromatin accessibility with transcriptional activity and to identify key transcription factors driving the observed gene expression changes. Results Analysis of striatum-specific transcriptome revealed significant upregulation of immune response genes, particularly type II interferon signaling, and downregulation of neural activation pathways. Analysis of striatum-specific epigenome showed increased chromatin accessibility at promoters of immune-related genes. Integrated analysis highlighted PU.1 as a key transcription factor in upregulated pathways, while neural pathways lacked epigenetic regulation, revealing distinct molecular responses in the striatum following chronic hypoperfusion. Conclusions Our findings indicate that upregulated pathways in the striatum following BCAS-induced CCH are driven by epigenetic changes, while downregulated pathways occur independently of these modifications. Additionally, PU.1 plays a critical role in mediating immune responses, offering a potential target for therapeutic intervention. |
| format | Article |
| id | doaj-art-93259403dfe84f839f6d93ade9e0cfb9 |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-93259403dfe84f839f6d93ade9e0cfb92025-01-26T12:16:26ZengBMCBMC Genomics1471-21642025-01-0126111410.1186/s12864-025-11256-yIntegrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in miceShijia Le0Fengyiyang Xu1Zhi Luo2Weihao Shi3Shuangshuang Lu4Zengyu Zhang5Zimin Guo6Wenshi Xu7Mingqi Yang8Tianyi Li9Xu Li10Kun Liang11Lei Zhu12Shanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityDepartment of Surgery, Shanghai Deji Hospital, Qingdao UniversityDepartment of Vascular Surgery, Huashan Hospital, Fudan UniversityDepartment of Radiology, Huashan Hospital, Fudan UniversityShanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityShanghai Medical College, Fudan UniversityDepartment of Vascular Surgery, Zhongshan Hospital, Institute of Vascular Surgery, National Clinical Research Center for Interventional Medicine, Fudan UniversityDepartment of Vascular Surgery, Huashan Hospital, Fudan UniversityDepartment of Vascular Surgery, Huashan Hospital, Fudan UniversityAbstract Background Vascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the striatum, a brain region critical for motor function and cognition, following chronic hypoperfusion using a bilateral common carotid artery stenosis (BCAS) model in mice. Methods RNA-seq was utilized to identify differentially expressed genes (DEGs) associated with hypoperfusion. In parallel, ATAC-seq was used to assess changes in chromatin accessibility within the striatum, providing insight into the epigenome and potential regulatory mechanisms. The integration of these datasets allowed us to correlate chromatin accessibility with transcriptional activity and to identify key transcription factors driving the observed gene expression changes. Results Analysis of striatum-specific transcriptome revealed significant upregulation of immune response genes, particularly type II interferon signaling, and downregulation of neural activation pathways. Analysis of striatum-specific epigenome showed increased chromatin accessibility at promoters of immune-related genes. Integrated analysis highlighted PU.1 as a key transcription factor in upregulated pathways, while neural pathways lacked epigenetic regulation, revealing distinct molecular responses in the striatum following chronic hypoperfusion. Conclusions Our findings indicate that upregulated pathways in the striatum following BCAS-induced CCH are driven by epigenetic changes, while downregulated pathways occur independently of these modifications. Additionally, PU.1 plays a critical role in mediating immune responses, offering a potential target for therapeutic intervention.https://doi.org/10.1186/s12864-025-11256-yChronic cerebral hypoperfusionBilateral carotid artery stenosisStriatumRNA-seqATAC-seq |
| spellingShingle | Shijia Le Fengyiyang Xu Zhi Luo Weihao Shi Shuangshuang Lu Zengyu Zhang Zimin Guo Wenshi Xu Mingqi Yang Tianyi Li Xu Li Kun Liang Lei Zhu Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice BMC Genomics Chronic cerebral hypoperfusion Bilateral carotid artery stenosis Striatum RNA-seq ATAC-seq |
| title | Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| title_full | Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| title_fullStr | Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| title_full_unstemmed | Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| title_short | Integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| title_sort | integrated analysis of chromatin and transcriptomic profiling of the striatum after cerebral hypoperfusion in mice |
| topic | Chronic cerebral hypoperfusion Bilateral carotid artery stenosis Striatum RNA-seq ATAC-seq |
| url | https://doi.org/10.1186/s12864-025-11256-y |
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